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https://www.readbyqxmd.com/read/27914004/hybrid-receptor-bound-mm-gbsa-per-residue-energy-based-pharmacophore-modelling-enhanced-approach-for-identification-of-selective-lta4h-inhibitors-as-potential-anti-inflammatory-drugs
#1
Patrick Appiah-Kubi, Mahmoud Soliman
Leukotriene A4 hydrolase has been identified as an enzyme with dual anti- and pro-inflammatory role, thus, the conversion of leukotriene to leukotriene B4 in the initiation stage of inflammation and the removal of the chemotactic Pro-Gly-Pro tripeptide. These findings make leukotriene A4 hydrolase an attractive drug target: suggesting an innovative approach towards the identification and design of novel class of compounds that can selectively inhibit leukotriene B4 synthesis while sparing the aminopeptidase activity...
December 2, 2016: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27913847/patulin-transformation-products-and-last-intermediates-in-its-biosynthetic-pathway-e-and-z-ascladiol-are-not-toxic-to-human-cells
#2
Joanna Tannous, Selma P Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, André El Khoury, Ali Atoui, Ting Zhou, Roger Lteif, Isabelle P Oswald, Olivier Puel
Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913844/global-dna-methylation-profiling-of-manganese-exposed-human-neuroblastoma-sh-sy5y-cells-reveals-epigenetic-alterations-in-parkinson-s-disease-associated-genes
#3
Prashant Tarale, Saravanadevi Sivanesan, Atul P Daiwile, Reinhard Stöger, Amit Bafana, Pravin K Naoghare, Devendra Parmar, Tapan Chakrabarti, Krishnamurthi Kannan
Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson's disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson's disease...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27913828/engineering-and-evolution-of-saccharomyces-cerevisiae-to-produce-biofuels-and-chemicals
#4
Timothy L Turner, Heejin Kim, In Iok Kong, Jing-Jing Liu, Guo-Chang Zhang, Yong-Su Jin
To mitigate global climate change caused partly by the use of fossil fuels, the production of fuels and chemicals from renewable biomass has been attempted. The conversion of various sugars from renewable biomass into biofuels by engineered baker's yeast (Saccharomyces cerevisiae) is one major direction which has grown dramatically in recent years. As well as shifting away from fossil fuels, the production of commodity chemicals by engineered S. cerevisiae has also increased significantly. The traditional approaches of biochemical and metabolic engineering to develop economic bioconversion processes in laboratory and industrial settings have been accelerated by rapid advancements in the areas of yeast genomics, synthetic biology, and systems biology...
December 3, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27913738/extracorporeal-membrane-oxygenation-in-transcatheter-aortic-valve-replacement
#5
Elena Dolmatova, Kasra Moazzami, Thomas P Cocke, Elie Elmann, Pranay Vaidya, Arthur F Ng, Kumar Satya, Rajeev L Narayan
BACKGROUND: Patients undergoing transcatheter aortic valve replacement can experience severe perioperative complications leading to hemodynamic instability and death. Venoarterial extracorporeal membrane oxygenation can be used to provide cardiorespiratory support during this time. METHODS: From 2012 to 2015, of 247 patients who underwent transcatheter aortic valve replacement, 6 (2.42%) required extracorporeal membrane oxygenation support. Their mean age was 82 ± 7...
December 2, 2016: Asian Cardiovascular & Thoracic Annals
https://www.readbyqxmd.com/read/27913677/phlpping-through-history-a-decade-in-the-life-of-phlpp-phosphatases
#6
REVIEW
Agnieszka T Grzechnik, Alexandra C Newton
In the decade since their discovery, the PH domain leucine-rich repeat protein phosphatases (PHLPP) have emerged as critical regulators of cellular homeostasis, and their dysregulation is associated with various pathophysiologies, ranging from cancer to degenerative diseases, such as diabetes and heart disease. The two PHLPP isozymes, PHLPP1 and PHLPP2, were identified in a search for phosphatases that dephosphorylate Akt, and thus suppress growth factor signaling. However, given that there are over 200 000 phosphorylated residues in a single cell, and fewer than 50 Ser/Thr protein phosphatases, it is not surprising that PHLPP has many other cellular functions yet to be discovered, including a recently identified role in regulating the epigenome...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913604/conversion-of-t-cells-to-b-cells-by-inactivation-of-polycomb-mediated-epigenetic-suppression-of-the-b-lineage-program
#7
Tomokatsu Ikawa, Kyoko Masuda, Takaho A Endo, Mitsuhiro Endo, Kyoichi Isono, Yoko Koseki, Rinako Nakagawa, Kohei Kometani, Junichiro Takano, Yasutoshi Agata, Yoshimoto Katsura, Tomohiro Kurosaki, Miguel Vidal, Haruhiko Koseki, Hiroshi Kawamoto
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913603/the-tumor-suppressor-flcn-mediates-an-alternate-mtor-pathway-to-regulate-browning-of-adipose-tissue
#8
Shogo Wada, Michael Neinast, Cholsoon Jang, Yasir H Ibrahim, Gina Lee, Apoorva Babu, Jian Li, Atsushi Hoshino, Glenn C Rowe, James Rhee, José A Martina, Rosa Puertollano, John Blenis, Michael Morley, Joseph A Baur, Patrick Seale, Zoltan Arany
Noncanonical mechanistic target of rapamycin (mTOR) pathways remain poorly understood. Mutations in the tumor suppressor folliculin (FLCN) cause Birt-Hogg-Dubé syndrome, a hamartomatous disease marked by mitochondria-rich kidney tumors. FLCN functionally interacts with mTOR and is expressed in most tissues, but its role in fat has not been explored. We show here that FLCN regulates adipose tissue browning via mTOR and the transcription factor TFE3. Adipose-specific deletion of FLCN relieves mTOR-dependent cytoplasmic retention of TFE3, leading to direct induction of the PGC-1 transcriptional coactivators, drivers of mitochondrial biogenesis and the browning program...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#9
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913582/bremsstrahlung-dose-yield-for-high-intensity-short-pulse-laser-solid-experiments
#10
Taiee Liang, Johannes M Bauer, James C Liu, Sayed H Rokni
A bremsstrahlung source term has been developed by the Radiation Protection (RP) group at SLAC National Accelerator Laboratory for high-intensity short-pulse laser-solid experiments between 10(17) and 10(22) W cm(-2) This source term couples the particle-in-cell plasma code EPOCH and the radiation transport code FLUKA to estimate the bremsstrahlung dose yield from laser-solid interactions. EPOCH characterizes the energy distribution, angular distribution, and laser-to-electron conversion efficiency of the hot electrons from laser-solid interactions, and FLUKA utilizes this hot electron source term to calculate a bremsstrahlung dose yield (mSv per J of laser energy on target)...
December 1, 2016: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#11
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913500/fitness-in-the-elderly-how-to-make-decisions-regarding-acute-myeloid-leukemia-induction
#12
Arati V Rao
Acute myeloid leukemia (AML) is a disease of the elderly, but less than half of these patients are offered therapy despite the evidence of better survival with treatment in this patient population. Assessing fit, vulnerable, and frail older adults with AML remains a challenge for the treating oncologist. A majority of AML patients are elderly and often have significant comorbidities, lack of social support, and older caregivers. Performance status (PS), a subjective measure of how a patient will tolerate cancer chemotherapy, has been strongly correlated with mortality in older AML patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913497/response-adapted-frontline-therapy-for-hodgkin-lymphoma-are-we-there-yet
#13
Peter W M Johnson
Treating Hodgkin lymphoma by using chemotherapy with or without radiotherapy is highly successful, with substantially fewer deaths from lymphoma than from other causes in recent studies of both early-stage and advanced-stage disease. Long-term toxicity is a major consideration in this context, and recent trials have used functional imaging with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography early in the course of treatment (interim PET) to assess response and modulate subsequent therapy. In early-stage disease, this has allowed omission of consolidation radiotherapy after a good response to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, and trials have shown that this can be done without detriment to overall survival, despite a small increase in rates of recurrence of ∼5%...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913475/molecular-monitoring-in-chronic-myeloid-leukemia-how-low-can-you-go
#14
Susan Branford
Molecular monitoring of BCR-ABL1 transcripts for patients with chronic myeloid leukemia (CML) is now used to assess response to tyrosine kinase inhibitors (TKIs), including treatment failure that mandates a change of therapy. Therefore, many centers have adopted the molecular technique for measuring BCR-ABL1 and rely on conversion of values to the international reporting scale for appropriate clinical interpretation. However, the technique has a degree of inherent variability despite standardized procedures, which means care should be taken by the clinician when assessing response based on BCR-ABL1 cutoff limits...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913451/treating-primary-dysmenorrhoea-with-acupuncture-a-narrative-review-of-the-relationship-between-acupuncture-dose-and-menstrual-pain-outcomes
#15
Mike Armour, Caroline A Smith
OBJECTIVE: A number of randomised controlled trials have been performed to determine the effectiveness or efficacy of acupuncture in primary dysmenorrhoea. The objective of this review was to explore the relationship between the 'dose' of the acupuncture intervention and menstrual pain outcomes. METHODS: Eight databases were systematically searched for trials examining penetrating body acupuncture for primary dysmenorrhoea published in English up to September 2015...
December 2016: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/27913445/rate-and-risk-factors-for-the-conversion-of-fovea-on-to-fovea-off-rhegmatogenous-retinal-detachment-while-awaiting-surgery
#16
Andreas Kontos, Tom H Williamson
BACKGROUND/AIMS: Progression of a fovea-on to a fovea-off rhegmatogenous retinal detachment (RRD) while awaiting surgery is rare. METHODS: A retrospective review of patient records to identify patients in whom a fovea-on retinal detachment at presentation was found to be fovea off at surgery. RESULTS: We identified 10 cases over 14 years which converted from fovea-on to fovea-off RRD while awaiting surgery. This represented 1.1% of RRDs that were fovea on at presentation (n=930)...
December 2, 2016: British Journal of Ophthalmology
https://www.readbyqxmd.com/read/27913413/new-arsenate-reductase-gene-arra-pcr-primers-for-diversity-assessment-and-quantification-in-environmental-samples
#17
Babur S Mirza, Darwin L Sorensen, R Ryan Dupont, Joan E McLean
: The extent of arsenic contamination in drinking water and its potential threat to human health have resulted in considerable research interest in the microbial species responsible for arsenic reduction. The arsenate reductase gene (arrA), an important component of the microbial arsenate reduction system, has been widely used as a biomarker to study arsenate reducing microorganisms. A new primer pair was designed and evaluated for qPCR and high-throughput sequencing of the arrA gene, because currently available PCR primers are not suitable for these applications...
December 2, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27913296/regulation-of-skeletal-muscle-insulin-stimulated-signaling-through-the-mek-redd1-mtor-axis
#18
Cory M Dungan, David L Williamson
Recent findings in adipocytes suggest that mitogen-activated protein kinase (MAPK)/extracellular-regulated signaling kinase (ERK) kinase 1/2 (MEK1/2) signaling regulates regulated in development and DNA damage 1 (REDD1) protein expression. Similarly, our previous work show that a lack of REDD1 protein expression, and associated hyperactive basal mechanistic target of rapamycin (mTOR) signaling, limits skeletal muscle's response to insulin. Therefore, we sought to determine: 1) if MEK1/2 inhibition is sufficient to reduce REDD1 protein expression and subsequently insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation via negative feedback of hyperactive mTOR in REDD1 wild-type (WT) mice and 2) if rapamycin-mediated mTOR inhibition is sufficient to improve IRS-1 tyrosine phosphorylation in REDD1 knockout (KO) mice...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913275/dietary-fish-oil-replacement-by-linseed-oil-effect-on-growth-nutrient-utilization-tissue-fatty-acid-composition-and-desaturase-gene-expression-in-silver-barb-puntius-gonionotus-fingerlings
#19
Madhusmita Nayak, Ashis Saha, Avinash Pradhan, Mrinal Samanta, Shiba Shankar Giri
Silver barb (Puntius gonionotus) is considered a promising medium carp species for freshwater aquaculture in Asia. This study in silver barb was carried out to evaluate the effects of total or partial substitution of dietary fish oil (FO) with linseed oil (LO) on growth, nutrient utilization, whole-body composition, muscle and liver fatty acid composition. Fish (12.1±0.4g of initial body weight) were fed for 60days with five experimental iso-proteinous, iso-lipidic and iso-caloric diets in which FO (control diet) was replaced by 33...
November 29, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27913246/measuring-content-overlap-during-handoff-communication-using-distributional-semantics-an-exploratory-study
#20
Joanna Abraham, Thomas Kannampallil, Vignesh Srinivasan, William Galanter, Gail Tagney, Trevor Cohen
OBJECTIVE: We develop and evaluate a methodological approach to measure the degree and nature of overlap in handoff communication content within and across clinical professions. This extensible, exploratory approach relies on combining techniques from conversational analysis and distributional semantics. MATERIALS AND METHODS: We audio-recorded handoff communication of residents and nurses on the General Medicine floor of a large academic hospital (n=120 resident and n=120 nurse handoffs)...
November 29, 2016: Journal of Biomedical Informatics
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